[unreadable] [unreadable] Sickle cell disease (SCD) affects approximately 91,000 Americans and probably about five million people worldwide. In just one generation, the median survival of patients with homozygous hemoglobin SS in the U.S. has increased from 14 years to nearly 50 years. As more and more patients with SCD survive longer, there remains a critical need to learn how to prevent and treat the increasing number of patients with endorgan damage resulting from SCD. Thus our specific aims are to: (1) Establish a Clinical Research Center in the SCD Clinical Research Network, comprising Duke and UNC Chapel Hill. East Carolina University will also participate on a capitated basis in clinical studies. Our mission is to promote and conduct all types of clinical research designed to develop new and improved treatments for SCD. Together these sites represent talented investigators, access to patient populations, and the infrastructure requisite to conduct high quality clinical research in SCD. These three institutions have a long history of collaborative research in SCD and an administrative structure to coordinate activities. (2) Participate in the SCD Clinical Research Network. This will include working with the Steering Committee and subcommittees of the network to ensure appropriate review of proposed studies from individual centers and development of common protocols for implementation. We will also work with the Outcomes Research Core, the Data Coordinating Center and the other Clinical Centers of the network to efficiently start and complete common clinical research trials at the Duke-UNC Center. We will accept awards for the support of research based on per-patient rates and the actual numbers of subjects who are enrolled and followed, and who complete each study. (3) Develop and propose multi-center clinical research trials designed to identify and validate therapeutic options in the treatment of SCD and its sequelae. Clinical trials will be developed by the PI and her co-investigators for submission to the network's Steering Committee. We have prepared two clinical research trials for this proposal. Study 1 will investigate whether cardiac remodeling due to the high output state of SCD can be slowed or reversed with angiotensin receptor blockade, thus improving cardiac reserve and preventing progression to high output heart failure. Study 2 is designed to investigate the utility of low intensity anticoagulation therapy to prevent vaso-occlusive episodes in patients with SCD. Additional studies will be proposed to the Network based on patient populations, feasibility, and impact on patient care. We also include in this application a proposal for a Patient Outcomes Research Core. The Duke-UNC SCD Clinical Research Center is committed to developing and conduction critically important clinical studies [unreadable] to improve prevention and treatment. We have the patient populations, strong clinical research experience and expertise, and talented investigators necessary to accomplish the goals of the Network. (End of Abstract) [unreadable] [unreadable] CLINICAL CENTER [unreadable] [unreadable] [unreadable]